title: Gleason pattern 5 is the strongest pathologic predictor of recurrence, metastasis, and prostate cancer-specific death in patients receiving salvage radiation therapy following radical prostatectomy.
abstract: BACKGROUND
  The presence of Gleason pattern 5 (GP5) at radical prostatectomy (RP) has been associated with worse clinical outcome; however, this pathologic variable has not been assessed in patients receiving salvage radiation therapy (SRT) after a rising prostate-specific antigen level.
  
  
  METHODS
  A total of 575 patients who underwent primary RP for localized prostate cancer and subsequently received SRT at a tertiary medical institution were reviewed retrospectively. Primary outcomes of interest were biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM), which were assessed via univariate analysis and Fine and Grays competing risks multivariate models.
  
  
  RESULTS
  On pathologic evaluation, 563 (98%) patients had a documented Gleason score (GS). The median follow-up post-SRT was 56.7 months. A total of 60 (10.7%) patients had primary, secondary, or tertiary GP5. On univariate analysis, the presence of GP5 was prognostic for BF (hazard ratio [HR] 3.3; P < .0001), DM (HR:11.1, P < .0001), and PCSM (HR:8.8, P < .0001). Restratification of the Gleason score to include GP5 as a distinct entity resulted in improved prognostic capability. Patients with GP5 had clinically worse outcomes than patients with GS8(4+4). On multivariate analysis, the presence of GP5 was the most adverse pathologic predictor of BF (HR 2.9; P < .0001), DM (HR 14.8; P < .0001), and PCSM (HR 5.7; P < .0001).
  
  
  CONCLUSIONS
  In the setting of SRT for prostate cancer, the presence of GP5 is a critical pathologic predictor of BF, DM, and PCSM. Traditional GS risk stratification fails to fully utilize the prognostic capabilities of individual Gleason patterns among men receiving SRT post-RP.
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: William
authors.initials: W
authors.lastname: Jackson
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hamstra
authors.forename: Skyler
authors.initials: S
authors.lastname: Johnson
authors.forename: Jessica
authors.initials: J
authors.lastname: Zhou
authors.forename: Benjamin
authors.initials: B
authors.lastname: Foster
authors.forename: Corey
authors.initials: C
authors.lastname: Foster
authors.forename: Darren
authors.initials: D
authors.lastname: Li
authors.forename: Yeohan
authors.initials: Y
authors.lastname: Song
authors.forename: Ganesh S
authors.initials: GS
authors.lastname: Palapattu
authors.forename: Lakshmi P
authors.initials: LP
authors.lastname: Kunju
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Feng
mesh_terms: D000368:Aged; D000728:Androgens / Q000172:deficiency; D001707:Biopsy, Needle; D006801:Humans; D007610:Kallikreins; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000532:radiotherapy* / Q000601:surgery; D012189:Retrospective Studies; D016879:Salvage Therapy; D016019:Survival Analysis
chemical_list: D000728:Androgens; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Gleason pattern; outcomes; prognosis; prostate cancer; salvage radiation therapy